Defining an abnormal p53 immunohistochemical stain in Barrett's oesophagus-related dysplasia: a single-positive crypt is a sensitive and specific marker of dysplasia.

AIMS: p53 is an independent risk stratification marker in Barrett's oesophagus (BE), but no universally accepted definition exists for abnormal p53 staining. Herein, we assess p53 stains in two cohorts to: (1) define abnormal p53 staining in BE-related dysplasia (BERD) and (2) assess the specificity and sensitivity of this cut-point for the diagnosis of dysplasia. METHODS: Cohort 1 (n = 313) included (1) dysplastic BE biopsies, (2) prior non-dysplastic BE (NDBE) biopsies from the same patients and (3) NDBE biopsies from patients who never progressed to dysplasia. Cohort 2 (n = 191) consisted of BE biopsies in which p53 staining aided in diagnosing dysplasia. Automated p53 staining quantification was performed on cohort 1. A semiquantitative p53 analysis, performed on both cohorts, included: (1) number of strongly positive glands, (2) strong glandular surface staining, (3) percentage of strongly positive glands and (4) null phenotype. RESULTS: NDBE biopsies from cohort 1 patients who progressed to dysplasia were more likely to show p53 positivity than non-progressors (16.9 versus 0.6%) (P = 0.0001). The optimal quantitative cut-point for distinguishing dysplastic from never-dysplasia biopsies was 10 strongly positive cells. By semiquantitative analysis, a single strongly p53-positive gland distinguished dysplastic from never-dysplasia BE (sensitivity 98.6%, specificity 99.4%). The semiquantitative and quantitative analyses correlated (P = 0.0001). In cohort 2, the sensitivity and specificity for BERD of ≥ 1 strongly positive p53 gland were 86.0 and 88.6%. CONCLUSIONS: A single strongly positive p53 gland is sensitive and specific for BERD. Automated p53 analysis may reduce subjectivity associated with the diagnosis of BERD.

Fine-needle aspiration of primary Langerhans cell histiocytosis of the thyroid gland, a potential mimic of papillary thyroid carcinoma.

BACKGROUND: The clinical presentation of Langerhans cell histiocytosis (LCH) as a primary solitary nodule in the thyroid gland is rare. As a result, there are few reports of its cytologic features in thyroid aspirates where it can pose a diagnostic pitfall. CASE AND CONCLUSION: To foster familiarity with its cytomorphology, we report the fine-needle aspiration biopsy (FNAB) findings of 3 specimens from 2 patients with LCH presenting as a solitary thyroid nodule. All aspirates contained numerous dispersed cells with prominent nuclear grooves, and the background showed a mixed pattern of chronic inflammation including scattered eosinophils. The aspirate from patient 1 raised a differential diagnosis that included chronic lymphocytic thyroiditis and a thyroglossal duct cyst, while the aspirate from patient 2 was interpreted as 'suspicious for papillary thyroid carcinoma'. The diagnosis of LCH was confirmed in both patients after lobectomy and immunohistochemical studies that revealed positive reactivity for CD1a and S-100. LCH of the thyroid gland is rare and can pose significant diagnostic challenges, but increased familiarity with its characteristic cytomorphology can help in avoiding diagnostic pitfalls.

Deep Herpes.

Herpes viruses are known for infecting epithelial cells and manifesting as vesicles. However, herpes viruses can also infect stromal cells. While established in the ocular setting, cutaneous stromal herpes (deep herpes) is previously unreported and may evade clinical and microscopic detection. We searched for skin biopsies with herpes stromal disease. Clinical information was retrieved via electronic medical records and pathology records system. Hematoxylin and eosin slides, immunohistochemical staining, and polymerase chain reaction detection of viral DNA was performed. We identified 12 specimens from 10 patients with cutaneous stromal herpes simplex virus 1/2 (n=7) or varicella-zoster virus infection (n=5). The most common site involved was the buttocks/perianal region (n=6). Ulceration was a frequent dermatologic finding (n=8). Pyoderma gangrenosum was clinically suspected in 6 specimens (50%). Eight patients (80%) were immunosuppressed. Biopsies frequently demonstrated a dense dermal mixed inflammatory infiltrate with subcutaneous extension and enlarged cells with viral cytopathic changes confirmed by herpes simplex virus 1/2 or varicella-zoster virus immunohistochemistry (n=10) or polymerase chain reaction (n=2). Most specimens (67%) lacked evidence of characteristic epidermal keratinocyte infection. This study presents the first known report of the ability of herpes virus to infect deep stromal cells of the dermis. We raise awareness of cutaneous stromal herpes in patients presenting with atypical clinical lesions, particularly while immunocompromised. Establishing the correct diagnosis is critical for initiating therapy.

An approach to post-radical trachelectomy vaginal-isthmus cytology.

Radical trachelectomy (RT) is the surgical amputation of the uterine cervix with paracervical lymphadenectomy, performed in reproductive age women to treat invasive squamous-cell carcinoma or endocervical adenocarcinoma while preserving the uterine corpus for potential child bearing. Post-RT patient monitoring includes isthmic-vaginal cytology. This study reviews our experience with liquid based preparation of post-RT cytology samples. Fifty-four post-RT vaginal-isthmic cytology specimens were reviewed from nine patients, seven with adenocarcinoma, and two with squamous-cell carcinoma. Five patients had normal (NILM) or normal with reactive changes on all cytology samples. Two patients had isolated squamous abnormalities (atypical squamous-cells of uncertain significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL)); both follow-up biopsies were negative. Two patients had repeatedly abnormal specimens interpreted as atypical glandular cells (AGC), one of whom also had a concurrent ASC-US. Only one sample was tested for high risk human papilloma virus (hrHPV), with negative results. All patients with abnormal cytology went on to have biopsies which were interpreted as benign. The cytology specimens most often interpreted as AGC contained many groups of hyperchromatic crowded glandular cells and/or stromal cells derived from direct sampling of the lower uterine segment. The crowding often limits visualization of all the cells in a group, plus sampled endometrium may harbor mitoses, adding to the atypical appearance. Cytologists should become familiar with the spectrum of changes in the post-RT cytology. Testing for hrHPV should be considered for use in the management of abnormal cytology results. Post RT cytology should be compared with presurgical cytology since one would anticipate similarities in post-RT true positive cases. In particular, a primary diagnosis of adenocarcinoma makes differentiating benign reactive glandular cells from recurrence a critical issue.

Measuring the clinical impact of pathologist reviews of blood and body fluid smears.

CONTEXT: Despite the widespread practice of pathologist review of blood and body fluid smears, little is known about its impact on improving patient care. OBJECTIVE: To assess the clinical usefulness of pathologist review of blood and body fluid smears. DESIGN: Survey study. Pathology residents contacted the ordering physician after pathologist reviews were reported to assess their clinical impact. RESULTS: Ninety-six pathologist reviews met criteria for study inclusion, and 64 ordering physicians were successfully contacted during the 2-month study period. Of the 64 cases, 19 reviews (30%) had been seen by the physician within 24 to 48 hours after the report was issued and 33 (51%) had not been seen; in 4 (6%) instances, physicians did not remember whether they had seen the review. Eight reviews (13%) were considered urgent enough to warrant immediate communication by the pathologist. Of the 27 reviews that were seen or directly communicated, 23 (85%) contributed to clinical diagnosis and/or patient management. CONCLUSIONS: This study demonstrates the contribution of pathologist reviews of blood and body fluids to clinical diagnosis and patient management. The results also highlight the problem of a lack of physician awareness of clinical pathology results.